multitargeting

Multitargeting refers to strategies or therapeutic agents that interact with two or more biological targets simultaneously. In pharmacology, it describes the design or use of a single compound or regimen that modulates multiple molecular pathways rather than a single target. This approach contrasts with traditional one-drug–one-target paradigms and is often described under the umbrella of polypharmacology or network pharmacology.

Rationale: Many diseases are multifactorial and involve interconnected signaling networks. By modulating several nodes at once, multitargeting aims to increase treatment efficacy, limit compensatory mechanisms that reduce effectiveness, and potentially reduce the emergence of resistance. It can also enable dose reduction for individual targets and create synergistic effects.

Approaches include designing single molecules with affinity for multiple targets, using drug combinations that collectively cover several pathways, and employing computational or phenotypic screening to identify compounds with desirable multi-target profiles. Methods such as structure-based design, ligand-based profiling, and network analysis guide multitargeting strategies.

Evaluation focuses on potency and selectivity across targets, pharmacokinetics, safety, and the risk of off-target effects. Regulatory considerations can be more complex for multi-target therapies, particularly when safety arises from interactions among targets. Clinical success depends on achieving a beneficial balance between efficacy and tolerability.

Examples include approved drugs such as imatinib, which inhibits BCR-ABL, PDGFR, and c-KIT, and sorafenib, which targets multiple kinases including RAF and VEGFR pathways. Multitargeting is active in oncology, neuroscience, and metabolic disease research, as well as in agricultural chemistry and material science, where multiple mechanisms may be exploited.

See also: polypharmacology; network pharmacology; combination therapy.